@article{mbs:/content/journal/jgv/10.1099/vir.0.031013-0, author = "Cohen, Meytal and Braun, Efrat and Tsalenchuck, Yael and Panet, Amos and Steiner, Israel", title = "Restrictions that control herpes simplex virus type 1 infection in mouse brain ex vivo", journal= "Journal of General Virology", year = "2011", volume = "92", number = "10", pages = "2383-2393", doi = "https://doi.org/10.1099/vir.0.031013-0", url = "https://www.microbiologyresearch.org/content/journal/jgv/10.1099/vir.0.031013-0", publisher = "Microbiology Society", issn = "1465-2099", type = "Journal Article", abstract = "Elucidating the cellular and molecular factors governing herpes simplex virus type 1 (HSV-1) neurotropism is a prerequisite for understanding HSV-1 encephalitis and for targeting HSV-1-derived vectors for gene transfer to the brain. Earlier we had described an ex vivo system of mouse brain slices and demonstrated a selective and unique infection pattern, mostly around the ventricles. Here, we examined tissue factors controlling HSV-1 infection of brain slices. We demonstrated that heparan sulphate, while an important factor, does not determine the infection pattern. Hyaluronic acid, but not collagen, appears to enhance HSV-1 brain infection. To investigate whether tissue distribution of viral receptors determines the infection pattern, we examined transcription of herpes virus entry mediator and nectin-1 receptor genes in infected and uninfected brain regions. Both the infected and the uninfected regions express the receptors. We also explored the influence of intra-cellular factors. HSV-1 does not preferentially infect proliferating cells in the brain slices, despite its predilection to the ventricular zones. To delineate the step at which the HSV-1 infection cascade is restricted, mRNA was isolated following tissue infection, and transcription of the immediate-early and late viral genes was evaluated. The results indicated that HSV-1 genes are not expressed in regions that do not express a viral reporter gene. Therefore, we conclude that tissue resistance to infection is associated with a block at or prior to the immediate-early mRNA synthesis. Taken together, using the ex vivo system of organotypic culture we describe here extra-cellular and intra-cellular restriction levels of HSV-1 brain infection.", }